Elevated CSF inflammatory markers in patients with idiopathic normal pressure hydrocephalus do not promote NKCC1 hyperactivity in rat choroid plexus

Background Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological condition of unresolved etiology characterized by a clinical triad of symptoms; gait disturbances, urinary incontinence, and cognitive deterioration. In the present study, we aimed to elucidate the molecular coupling between inflammatory markers and development of iNPH and determine whether inflammation-induced hyperactivity of the choroidal Na+/K+/2Cl− cotransporter (NKCC1) that is involved in cerebrospinal fluid (CSF) secretion could contribute to the iNPH pathogenesis. Methods Lumbar CSF samples from 20 iNPH patients (10 with clinical improvement upon CSF shunting, 10 without clinical improvement) and 20 elderly control subjects were analyzed with the novel proximity extension assay technique for presence of 92 different inflammatory markers. RNA-sequencing was employed to delineate choroidal abundance of the receptors for the inflammatory markers found elevated in the CSF from iNPH patients. The ability of the elevated inflammatory markers to modulate choroidal NKCC1 activity was determined by addition of combinations of rat version of these in ex vivo experiments on rat choroid plexus. Results 11 inflammatory markers were significantly elevated in the CSF from iNPH patients compared to elderly control subjects: CCL28, CCL23, CCL3, OPG, CXCL1, IL-18, IL-8, OSM, 4E-BP1, CXCL6, and Flt3L. One inflammatory marker, CDCP1, was significantly decreased in iNPH patients compared to control subjects. None of the inflammatory markers differed significantly when comparing iNPH patients with and without clinical improvement upon CSF shunting. All receptors for the elevated inflammatory markers were expressed in the rat and human choroid plexus, except CCR4 and CXCR1, which were absent from the rat choroid plexus. None of the elevated inflammatory markers found in the CSF from iNPH patients modulated the choroidal NKCC1 activity in ex vivo experiments on rat choroid plexus. Conclusion The CSF from iNPH patients contains elevated levels of a subset of inflammatory markers. Although the corresponding inflammatory receptors are, in general, expressed in the choroid plexus of rats and humans, their activation did not modulate the NKCC1-mediated fraction of choroidal CSF secretion ex vivo. The molecular mechanisms underlying ventriculomegaly in iNPH, and the possible connection to inflammation, therefore remains to be elucidated.

Clinical characteristics and outcome of hydrocephalus in neurosarcoidosis: a retrospective cohort study and review of the literature

Hydrocephalus is reported in approximately one-tenth of neurosarcoidosis patients. However, data on clinical characteristics and outcome are lacking. In this retrospective study, we present 11 patients with neurosarcoidosis and hydrocephalus on neuroimaging. Median age was 52 years and seven were female (64%). Presenting symptoms consisted of headache in 8 out of 11 (73%), vertigo in 5 (46%), gait abnormalities in 4 (36%), diplopia in 2 (18%) and decreased visual acuity in 1 (9%). Cranial imaging showed obstructive hydrocephalus in 10 (91%) and non-obstructive hydrocephalus in 1 (9%) out of 11, obstruction occurred at the level of the fourth ventricle in 6 out of 10 (60%). Treatment consisted of glucocorticoids in all the patients with additional methotrexate or azathioprine in 6 (55%) and infliximab in 1 (9%) patient. Neurosurgical intervention was performed in 10 out of 11 (91%) patients. Treatment led to remission, improvement or stabilization of disease in 9 out of 10 (90%) of patients. One patient died due to cerebral herniation despite neurosurgical decompression and CSF shunting. Median modified Rankin scale score at last follow-up was 2 (range 0–6). A systematic review and meta-analysis of studies on hydrocephalus due to neurosarcoidosis identified 36 patients that compared to our patients had a lower median age at onset and a higher mortality. Acute obstructive hydrocephalus due to neurosarcoidosis is a potentially fatal medical emergency requiring neurosurgical intervention and initiation of immunosuppressive therapy. If patients survive the initial phase, the outcome is generally favorable.

Cerebrospinal fluid shunting protocol for idiopathic intracranial hypertension for an improved revision rate

OBJECTIVE Cerebrospinal fluid (CSF) shunting in idiopathic intracranial hypertension (IIH) is associated with high complication rates, primarily because of the technical challenges that are related to small ventricles and a large body habitus. In this study, the authors report the benefits of a standardized protocol for CSF shunting in patients with IIH as relates to shunt revisions. METHODS This was a retrospective study of consecutive patients with IIH who had undergone primary insertion of a CSF shunt between January 2014 and December 2020 at the authors’ hospital. In July 2019, they implemented a surgical protocol for shunting in IIH. This protocol recommended IIH shunt insertion by neurosurgeons with expertise in CSF disorders, a frontal ventriculoperitoneal (VP) shunt with an adjustable gravitational valve and integrated intracranial pressure monitoring device, frameless stereotactic insertion of the ventricular catheter, and laparoscopic insertion of the peritoneal catheter. Thirty-day revision rates before and after implementation of the protocol were compared in order to assess the impact of standardizing shunting for IIH on shunt complications. RESULTS The 81 patients included in the study were predominantly female (93%), with a mean age of 31 years at primary surgery and mean body mass index (BMI) of 37 kg/m2. Forty-five patients underwent primary surgery prior to implementation of the protocol and 36 patients after. Overall, 12 (15%) of 81 patients needed CSF shunt revision in the first 30 days, 10 before and 2 after introduction of the protocol. This represented a significant reduction in the early revision rate from 22% to 6% after the protocol (p = 0.036). The most common cause of shunt revision for the whole cohort was migration or misplacement of the peritoneal catheter, occurring in 6 of the 12 patients. Patients with a higher BMI were significantly more likely to have a shunt revision within 30 days (p = 0.022). CONCLUSIONS The Birmingham standardized IIH shunt protocol resulted in a significant reduction in revisions within 30 days of primary shunt surgery in patients with IIH. The authors recommend standardization for shunting in IIH as a method for improving surgical outcomes. They support the notion of subspecialization for IIH shunts, the use of a frontal VP shunt with sophisticated technology, and laparoscopic insertion of the peritoneal end.

Pediatric shunt revision analysis within the first year of shunt placement: A single center experience

Background: Hydrocephalus is a common problem in neurosurgery with shunt placement remains the mainstay of the management. However, shunt placement generally requires following surgical procedures, including shunt revision. Despite the recent developments, the incidence of shunt failure remains high, approximately 30–51% in the 1st year following the shunt placement. Methods: An observational retrospective study of pediatric neurosurgery patients whom underwent CSF shunting procedure, both primary and repeated VPS, VAS, CPS, and subdural-peritoneal shunt procedures between January 2018 and May 2019. The patients were observed for 12 months for potential complication requiring shunt revision following the shunt placement. Results: A total of 142 patients underwent shunt placement. The shunt revision within 12 months was found in 26 patients (18.3%), 25 cases were VPS (96.2%) and one case was CPS (3.8%). The mean period of time between shunt placement to shunt revision was 3.96 months. Age of under 6 months old during the shunt placement showed significantly higher risk for shunt revision (RR 2.32 CI 1.13–4.74, P = 0.018). The most common diagnosis requiring shunt revision was congenital anomaly (16 cases, 61.5%). The most common cause of revision was shunt malfunction, with 21 cases (80.8%) followed by infected shunt with 5 cases (19.2%). Conclusion: The 1st year observation showed relatively high rate for shunt revision. The patient underwent shunt procedure should be regularly followed up in long period for better evaluation of the outcome. The application of shunt registry in some countries appears to be efficient and beneficial for sustainable follow-up in patients underwent shunt placement.

Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus

Background: The amyloid-β oligomers, consisting of 10–20 monomers (AβO10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. Objective: We hypothesized that cerebrospinal fluid (CSF) AβO10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. Methods: We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10–20 levels at baseline, 1 and 3 years after shunting. Results: Cohort-1 had higher CSF AβO10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10–20 decrease showed better cognitive outcome than those without. Conclusion: AβO10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10–20 can be an applicable diagnostic and prognostic biomarker.

Endoscopic antegrade aqueductoplasty and stenting with panventricular catheter in management of trapped fourth ventricle in patients with inadequately functioning supratentorial shunt

Background: Trapped fourth ventricle (TFV) usually develops as a complication of supratentorial ventricular CSF shunting, especially when hydrocephalus is caused by intraventricular hemorrhage and/or infection. This study aimed to assess the feasibility of endoscopic aqueduct stenting using a single refashioned shunt tube to treat cases presenting with both TFV and shunt malfunction. Methods: We retrospectively collected and analyzed data from patients presenting with TFV and supratentorial shunt malfunction who underwent endoscopic aqueduct stenting using a refashioned shunt tube. All cases were treated at our institution between January 2010 and July 2019. The surgical technique is described. Results: Eighteen patients were enrolled in our study. There were ten males and eight females. The mean age was 11.2 years (range = 1–33 years). Headache, nausea, and vomiting were the most common clinical presentations. The mean duration of follow-up was 22.1 months (range = 6–60 months). All cases showed clinical and radiological improvement after surgery. Conclusion: Endoscopic antegrade aqueductoplasty and stenting with the refashioned panventricular shunt catheter are an adequate treatment option for both TFV and supratentorial shunt malfuncion.

Cerebrospinal fluid levels of amyloid-beta oligomers in patients with idiopathic normal pressure hydrocephalus are elevated before shunt surgery but decrease afterward

Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.

A Comparison of Ventriculoperitoneal and Ventriculoatrial Shunts in a Population of 544 Consecutive Pediatric Patients

BACKGROUND Although ventriculoperitoneal shunts (VPS) remain the first-line option in most instances of pediatric hydrocephalus, the long-term efficacy of ventriculoatrial shunts (VAS) remains unknown. OBJECTIVE To characterize the long-term outcomes and adverse occurrences associated with both VPS and VAS at our institution. METHODS The authors retrospectively analyzed all cerebrospinal fluid (CSF) shunting procedures performed over a 13-yr period at a single institution. A total of 544 pediatric shunt patients were followed for at least 90 d (VPS: 5.9 yr; VAS: 5.3 yr). RESULTS A total of 54% of VPS and 60% of VAS required at least 1 revision. VPS demonstrated superior survival overall; however, if electively scheduled VAS lengthening procedures are not considered true “failures,” no statistical difference is noted in overall survival (P = .08). VPS demonstrated significantly greater survival in patients less than 7 yr of age (P = .001), but showed no difference in older children (P = .4). VAS had a significantly lower rate of infection (P < .05) and proximal failure (P < .001). CONCLUSION VAS can be a useful alternative to VPS when the abdomen is unsuitable, particularly in older children. Although VPS demonstrates superior overall survival, it should be understood that elective VAS lengthening procedures are often necessary, especially in younger patients. If elective lengthening procedures are not considered true failures, then the devices show similar survival.